Reactivity of a new family of diamido-diamine cyclam-based zirconium complexes in ethylene polymerization

Compounds of general formula [(^∗Bn₂Cyclam)ZrCl₂] (^∗Bn = 4-^tBuC₆H₄CH₂, (4) and 4-CF₃C₆H₄CH₂, (5)) were synthesised using Zr(CH₂SiMe₃)₂Cl₂(Et₂O)₂ and the corresponding ligand precursors 1,8-(4-^tbutylbenzyl)-1,4,8,11-tetraazacyclotetradecane (H₂(4-^tBuBn)₂Cyclam), (4a), and 1,8-(4-trifluoromethylbenzyl)-1,4,8,11-tetraazacyclotetradecane (H₂(4-CF₃Bn)₂Cyclam), (5a). Complexes 4 and 5, in addition to other [(^∗Bn₂Cyclam)ZrCl₂] compounds previously described by some of us (^∗Bn = PhCH₂, (1), 3,5-Me₂C₆H₃CH₂, (2) and 3,5-^tBu₂C₆H₃CH₂, (3)) were tested in the polymerization of ethylene in the presence of MAO. System 4/MAO presents the highest activity (2790 g PE molZr⁻¹ h⁻¹ atm⁻¹). The polymers formed are slight to moderately branched polyethylenes with a percentage of branching ranging between 1.2% and 3.3%. The melting points obtained by differential scanning calorimetry (DSC) ranging from 128 to 140 °C, are consistent with rather high average molecular weight polymers with crystallinity close to 50%.     

Binuclear manganese(III) complexes of an unsymmetric pyrazolate-based compartmental ligand with hard donor set

The synthesis, crystal structure and magnetic properties of manganese(III) binuclear complexes [Mn^III₂(L-3Н)₂(CH₃ОH)₄]·2CH₃ОH (1) and [Mn^III₂(L-3Н)₂(Py)₄]·2Py (2) (L = 3-[(1E)-N-hydroxyethanimidoyl]-4-methyl-1H-pyrazole-5-carboxylic acid) are reported. The ligand contains two distinct donor compartments formed by the pyrazolate-N and the oxime or the carboxylic groups. The complexes were characterized by X-ray single crystal diffraction, revealing that both 1 and 2 consist of dinuclear units in which the two metal ions are linked by double pyrazolate bridges with a planar {Mn₂N₄} core. Cryomagnetic measurements show antiferromagnetic interaction with g = 1.99, J = −3.6 cm⁻¹, Θ = −2.02 K for 1 and g = 2.00, J = −3.7 cm⁻¹, Θ = 1.43 K for 2.     

Synthesis and characterization of Ru(arene) complexes of bispyrazolylazines: Catalytic hydrogen transfer of ketones

The bis(pyrazol-1-yl)azine ligands 2,3-bis(pyrazol-1-yl)quinoxaline (bpzqnx), 2,3-bis(pyrazol-1-yl)pyrazine (bpzprz) and 3,6-bis(3,5-dimethylpyrazol-1-yl)pyridazine (bpz*pdz) were prepared by the reaction of pyrazolate salts and the corresponding azine dichloride derivatives. The reaction of these ligands with Ru(arene) precursors led to the mononuclear complexes [RuCl(arene)(L)]BPh₄ (arene = p-cymene, L = bpzqnx, 1, bpzprz, 5, bpz*pdz, 7; arene = C₆H₆, L = bpzqnx, 2, bpzprz, 6, bpz*pdz, 8) with the N-donor ligand coordinated in a bidentate chelate way. In general, the ligands coordinate through one pyrazole ring and the azine, except in the cases of 1 and 2 where the two pyrazolyl rings are coordinated to the metal in a symmetrical way. When the reactions between the ruthenium precursors and bpzqnx are carried out in MeOH, the complexes [RuCl(arene)(OMepzqnx)]BPh₄ with partially methanolyzed ligands are isolated (arene = p-cymene, 3; C₆H₆, 4). In this process a methoxy group has replaced one of the pyrazole groups in the ligand. The X-ray structures of 6 and 7 have been determined. These compounds have a three-legged piano-stool structure with cations and anions packed through weak interactions. Complexes 1-8 are active in ketone hydrogenation transfer processes even in the absence of base.     

Design,synthesis and biological evaluation of bitopic arylpiperazine-hexahydro-pyrazinoquinolines as preferential dopamine D3 receptor ligands

Three series of bitobic arylpiperazine-phenyl-hexahydropyrazinoquino- lines analogues were designed, synthesizedand evaluated as a novel class of selective ligands for the dopamine D3 receptor. Compounds 15a (K_i of 11.7 ± 1.8 and 373 nM at D3 and D2, respectively), 15c (K_i of 5.49 and 264 nM at D3 and D2, respectively), 15e (K_i of 14.9 and 325 nM at D3 and D2, respectively), 15i (K_i of 13.8 and 401 nM at D3 and D2, respectively) and 15l (K_i of 13.6 and 870 nM at D3 and D2, respectively) were found to demonstrate good binding affinity and selectivity, and especially compound 15c showeda similar binding affinity and selectivity compared with the contrast drug BP897.     

Syntheses and β‐adrenergic binding affinities of (R)‐ and (S)‐fluoronaphthyloxypropanolamines

The β‐adrenergic receptors mediate several physiological processes including heart rate (β₁), bronchodilation (β₂), and lipolysis (β₃). Therefore, selectivity is important for a possible therapeutic agent acting via these receptors. Aryloxypropanolamines are β‐receptor agonists or antagonists, depending on the aryl group and its substituents. We therefore hypothesized that fluorine substitution on the aromatic ring in this class could lead to significant biological effects because of the unique chemical characteristics of fluorine. Because the target compound has a chiral center, we set out to synthesize the two enantiomers so that effects of stereochemistry on biological activity could be evaluated. Syntheses of the enantiomers were performed starting with commercially available fluoronaphthalene and subsequent use of the chiral synthon (2R)‐ or (2S)‐glycidyl 3‐nitrobenzenesulfonate, depending on the desired enantiomer. High‐pressure liquid chromatography (HPLC) methods were used to characterize %ee. Each enantiomer was synthesized. They exhibited nanomolar binding activities on β‐adrenergic receptors. The (S)‐enantiomer was found to be up to 310 times more potent than the (R). It was also found to be about five‐fold more selective for β₂‐ than for β₁‐receptors. The current report demonstrates the importance of stereochemistry for the fluoroaromatic β‐receptor ligands. Chirality 11:144–148, 1999. © 1999 Wiley‐Liss, Inc.     

[Ni(L)(MeCN)]complex cation as a template for the assembly of extended I3 · I5 and I5 · I7 polyiodide networks {L=2,5,8-trithia[9](2,9)-1,10-phenanthrolinophane}. Synthesis and structures of [Ni(L)(MeCN)]I8 and [Ni(L)(MeCN)]I12

The compounds [Ni(L)(MeCN)]I₈ (1) and [Ni(L)(MeCN)]I₁₂ (2) have been obtained from the reactions of the complexes [Ni(L)(L^′)][BF₄]_(2 + n) {L=2,5,8-trithia[9](2,9)-1,10-phenanthrolinophane; L^′=MeCN, Cl⁻, Br⁻, I⁻; n=charge of L^′} with an excess of I₂ (molar ratios of 6, 10 and 20 have been used), in the presence of the stoichiometric amount of I⁻ (as Bu₄ⁿNI) necessary to balance the charge of the complex cation [Ni(L)(L^′)]^(2 + n)+. An X-ray diffraction analysis shows that, independently of the nature of L^′, both 1 and 2 contain the complex cation [Ni(L)(MeCN)]²⁺, which is therefore capable of templating two different polyiodide networks based on interacting I₃⁻/I₅⁻ and I₅⁻/I₇ units, respectively. The solid state FT-Raman spectra of 1 and 2 are discussed based on their structural features.     

Synthesis, characterization and supramolecular structures of two Ni(II) complexes with potentially heptadentate ligand N,N-bis(2-hydroxybenzyl)-1,3-bis[(2-aminoethyl)amino]-2-propanol

A potentially heptadentate ligand H₃L (N,N^′-bis(2-hydroxybenzyl)-1,3-bis[(2-aminoethyl)amino]-2-propanol) and its two Ni(II) complexes, [Ni(H₂L)H₂O](H₂O)₃ClO₄ (1) and [Ni(H₂L)(H₂O)](H₂O)Cl (2) were prepared and characterized. X-ray structural analyses indicate that complex 1 has a distorted octahedral coordination geometry, with four amine N atoms of H₂L⁻ defining the equatorial plane, one aqua O atom and one phenoxo O atom of the ligand occupying two axial positions, respectively. The Ni(II) center of 2 has coordination geometry similar to that of 1. IR and electronic spectra of 1 and 2 are in agreement with their crystal structural features. Approximately along the ab plane, 2D supramolecular structure of 1 is assembled through multiple hydrogen bonds between hydroxy groups of the ligands, coordinated and crystal lattice H₂O and π-π stacking interactions between adjacent phenyl rings of the ligands, while for that of 2, probably along the a axis, 1D chain structure is also formed by multiple hydrogen bonds, but lack of π-π stacking interactions.     

Discovery of tetrahydroisoquinoline-based bivalent heterodimeric IAP antagonists

Bivalent heterodimeric IAP antagonists that incorporate (R)-tetrahydroisoquinoline in the P3′ subunit show high affinity for the BIR2 domain and demonstrated potent IAP inhibitory activities in biochemical and cellular assays. Potent in vivo efficacy was observed in a variety of human tumor xenograft models. The bivalent heterodimeric molecule 3 with a P3–P3′ benzamide linker induced pharmacodynamic markers of apoptosis and was efficacious when administered intravenously at a dose of 1 mg/kg to mice harboring A875 human melanoma tumors. Analog 5, with a polyamine group incorporated at the P2′ thiovaline side chain exhibited antiproliferative activity against the P-gp expressing HCT116/VM46 cell line.     

Steric and counterion effects on the structure of dipicolylamine nickel complexes

Four nickel complexes each containing an R-2,2′-dipicolylamine ligand species (RDPA; R = benzyl, isopropyl, or tert-butyl) were synthesized and structurally characterized. In the absence of an interfering coordinating counterion, BzDPA and iPrDPA form 1:2 nickel:ligand complexes, with two facial ligands completing an pseudooctahedral nickel(II) coordination environment. In contrast, the sterically hindered tBuDPA ligand instead forms 1:1 metal:ligand complexes, even in the absence of associating counterions. Two novel tBuDPA nickel complexes with different counterions are described: nickel(II) chloride gives rise to an unusual 2Ni-3Cl dimer complex, while nickel(II) nitrate affords a 1:1 nickel:ligand complex which crystallizes with both fac and mer conformations in the same unit cell.     

Indole-3-piperazinyl derivatives: novel chemical class of 5-HT(6) receptor antagonists

N₁-Arylsulfonyl-3-piperazinyl indole derivatives were designed and identified as a novel class of 5-HT₆ receptors ligands. All the compounds have high affinity and antagonist activity towards 5-HT₆ receptor. The compound 7a (K_i = 3.4 nM, functional assay IC₅₀ = 310 nM) shows enhanced cognitive effect when tested in NORT and Morris water maze models. Synthesis, SAR and PK profile of these novel compounds constitute the subject matter of this Letter.